The Ion Transport Core facility will make readily available to Cystic Fibrosis (CF) Investigators, the assessment of Cl permeability needed to evaluate the functional expression of specific gene products in an experimental setting. Experimental preparations will include cultured epithelial cells, with or without the CF defect as well as cells in which an attempt has been made to correct the CF defect. Such preparations will also include clinical samples from CF patients once the Human Studies portion of the Gene Therapy for CF Lung Disease program is underway. It has been well established that an important manifestation of the CF mutation is abnormal regulation of chloride transport in a number of epithelial tissues, with the most obvious clinical effects occurring as a consequence of abnormal mucus production within the airways and the biliary system. It is also now well established that the most common defects leading to clinical CF result from expression of a specifically mutated chloride conductance pathway (CFTR), resulting in altered regulation of chloride conductance by epithelial cells. In some cases, this defect results from a functional CFTR which is not adequately transported to the membrane. In other cases it results from expression of a nonfunctioning CFTR. The core will provide those assays necessary to evaluate chloride transport in epithelial cells, allowing comparison between cells expressing normal or mutant CFTRs and also demonstrating functional reconstitution of normal CFTR as a consequence of gene therapy. While initially the core will focus on cultured cell lines, once gene therapy of patients begins, clinical specimens (epithelial cells) obtained via bronchoscopy or brushing will also be evaluated with respect to the presence or absence of normal CFTR. The core will also facilitate the development of new approaches to evaluating CFTR under special circumstances to accommodate the needs of investigators or pilot projects. Examples of novel approaches anticipated include fiberoptic evaluation of CFTR in situ in the in vivo xenograft model or in whole organ cultures (e.g. embryonic mouse lung). Finally, the core will be available to image fluorescent measurements of other important ions including calcium and protons as well as effects on membrane potential, which may be altered as result of genetically-induced alterations in the expression of CFTR.